Crystallization of paracetamol from ethanol-water solutions in the presence of polymers.

Abstract

We have examined the effect of polymer nature and concentration on yield and micromeritic, melting and compression properties of paracetamol crystals obtained from ethanol-water solutions using the solvent-change technique. Agar, gelatin, polyethylene-glycol (PEG) and polyvinylpyrrolidone (PVP) were the polymers used. These four polymers have different solubility in ethanol and water. It was found that the yield of crystallization may increase by up to 8% with agar, gelatin and PEG, polymers that are insoluble in ethanol, while the soluble PVP reduces yield by 14%. The size of crystals increased due to the addition of polymers and changed almost in parallel with the crystal yield for agar and gelatin. Gelatin resulted in the biggest crystals, agar in the most equidimensional (aspect ratio 1.45 and roundness 1.47) and PVP in the most elongated (aspect ratio 1.89 and roundness 2.13). PEG resulted in the most agglomerated crystals. Yield pressure, Py, decreased in the following order: agar > PEG > gelatin > PVP, which is the same order for the enthalpy of fusion. Gelatin and PEG significantly decreased the elastic recovery of tablets (0.05 level), probably due to plastic deformation of crystals and fragmentation of agglomerates, respectively. Crystallization of paracetamol in the presence of polymers by the solvent-change (ethanol-water) technique may permit increase of crystal yield, alteration of crystal shape and improvement of compression behaviour during tableting.